Before the coronavirus 2019 (COVID-19) pandemic began, antimicrobial resistance (AMR) was among the top priorities for global public health. Already a complex challenge, AMR now needs to be addressed in a changing healthcare landscape. Here, we analyse how changes due to COVID-19 in terms of antimicrobial usage, infection prevention, and health systems affect the emergence, transmission, and burden of AMR. Increased hand hygiene, decreased international travel, and decreased elective hospital procedures may reduce AMR pathogen selection and spread in the short term. However, the opposite effects may be seen if antibiotics are more widely used as standard healthcare pathways break down. Over 6 months into the COVID-19 pandemic, the dynamics of AMR remain uncertain. We call for the AMR community to keep a global perspective while designing finely tuned surveillance and research to continue to improve our preparedness and response to these intersecting public health challenges.
Glycosylation is one of the most prevalent post-translational modifications of a protein, with a defining impact on its structure and function. Many of the proteins involved in the innate or adaptive immune response, including cytokines, chemokines, and antimicrobial peptides (AMPs), are glycosylated, contributing to their myriad activities. The current availability of synthetic coupling and glycoengineering technology makes it possible to customise the most beneficial glycan modifications for improved AMP stability, microbicidal potency, pathogen specificity, tissue or cell targeting, and immunomodulation.
TLRs mediate recognition of a wide range of microbial products, including LPS, lipoproteins, flagellin, and bacterial DNA, and signaling through TLRs leads to the production of inflammatory mediators. In addition to TLRs, many other surface receptors have been proposed to participate in innate immunity and microbial recognition, and signaling through some of these, for example, C-type lectins, is likely to cooperate with TLR signaling in defining inflammatory responses. In the present study, we examined the importance of the ECD and intracellular TIR domain of boTLR2 and huTLR2 to induce a species-specific response by creating a chimeric TLR2 protein. Our results indicate that the strength of the response to any TLR2 ligand tested was dependent on the extracellular, solenoid structure, but not the intracellular TIR domain. Furthermore, we examined whether the recognition of two PAMPs by Dectin-1, a CLR, depends on the interaction with TLR2 from the same species. TLR2 expression seemed to affect the Dectin-1-dependent production of CXCL8 to β-glucan containing zymosan as well as Listeria monocytogenes. Furthermore, the interaction of Dectin-1 with TLR2 seemed to require that both receptors are from the same species. Our data demonstrate that the differences in the TLR2 response seen between the bovine and human system depend on the ECD of TLR2 and that collaborative recognition of distinct microbial components by different classes of innate-immune receptors is crucial in orchestrating inflammatory responses.
The Burkholderia genus contains a group of soil-dwelling Gram-negative organisms that are prevalent in warm and humid climates. Two species in particular are able to cause disease in animals, B. mallei primarily infects Equus spp. and B. pseudomallei (BPS), that is able to cause potentially life-threatening disease in humans. BPS is naturally resistant to many antibiotics and there is no vaccine available. Although not a specialised human pathogen, BPS possesses a large genome and many virulence traits that allow it to adapt and survive very successfully in the human host. Key to this survival is the ability of BPS to replicate intracellularly. In this review we highlight recent advances in our understanding of the intracellular survival of BPS, including how it overcomes host immune defenses and other challenges to establish its niche and then spread the infection. Knowledge of these mechanisms increases our capacity for therapeutic interventions against a well-armed foe.
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